[Jan. 17, 2024: JJ Shavit, The Brighter Side of News]
The formation of amyloid plaques in the brain is a hallmark of Alzheimer’s disease. (CREDIT: Creative Commons)
Alzheimer's disease is a debilitating neurodegenerative disorder that affects millions of people worldwide. It is characterized by the accumulation of amyloid plaques in the brain, which are thought to be the cause of the disease's hallmark symptoms.
Despite years of research, drugs designed to reduce the accumulation of these plaques have yielded, at best, mixed results in clinical trials. However, a new study from researchers at Yale University may have identified a new biomarker and potential therapeutic target for Alzheimer's disease.
The research team, led by Dr. Jaime Grutzendler, the Dr. Harry M. Zimmerman and Dr. Nicholas and Viola Spinelli Professor of Neurology and Neuroscience at the Yale School of Medicine, found that swelling caused by a byproduct of amyloid plaques may be the true cause of the disease's debilitating symptoms. Their findings were published in the journal Nature.
The researchers discovered that each formation of plaque can cause an accumulation of spheroid-shaped swellings along hundreds of axons, which are the thin cellular wires that connect the brain's neurons, near amyloid plaque deposits.
These swellings are caused by the gradual accumulation of organelles within cells known as lysosomes, which digest cellular waste. As the swellings enlarge, they can blunt the transmission of normal electrical signals from one region of the brain to another.
The pileup of lysosomes causes swelling along axons, which, in turn, triggers the devastating effects of dementia. "We have identified a potential signature of Alzheimer's which has functional repercussions on brain circuitry, with each spheroid having the potential to disrupt activity in hundreds of neuronal axons and thousands of interconnected neurons," said Dr. Grutzendler.
Further, the researchers discovered that a protein in lysosomes called PLD3 caused these organelles to grow and clump together along axons, eventually leading to the swelling of axons and the breakdown of electrical conduction.
When they used gene therapy to remove PLD3 from neurons in mice with a condition resembling Alzheimer's disease, they found that this led to a dramatic reduction of axonal swelling. This, in turn, normalized the electrical conduction of axons and improved the function of neurons in the brain regions linked by these axons.
The researchers say PLD3 may be used as a marker in diagnosing the risk of Alzheimer's disease and provide a target for future therapies. "It may be possible to eliminate this breakdown of the electrical signals in axons by targeting PLD3 or other molecules that regulate lysosomes, independent of the presence of plaques," said Dr. Grutzendler.
Swelling surrounding amyloid plaques (light blue) in Alzheimer’s patients may be a culprit in dementia symptoms. (CREDIT: Yale University)
Alzheimer's disease is a devastating illness that affects millions of people worldwide. Currently, there is no cure, and available treatments can only help to manage symptoms.
However, the discovery of a new biomarker and potential therapeutic target for the disease is a significant step forward in the fight against Alzheimer's. The research team's findings provide hope for the development of new treatments that could improve the quality of life for those living with the disease.
The next step for the researchers is to further explore the role of PLD3 in Alzheimer's disease and to investigate other molecules that regulate lysosomes. They hope that their work will lead to the development of new therapies that can target the root cause of the disease, rather than just managing its symptoms.
The discovery of a new biomarker and potential therapeutic target for Alzheimer's disease is a significant breakthrough in the field of neurodegenerative disorders. It provides hope for the development of new treatments that could improve the lives of millions of people affected by the disease.
The researchers' findings represent a step forward in our understanding of the complex mechanisms underlying Alzheimer's disease, which has long been considered one of the most challenging and enigmatic conditions in medicine.
Who has Alzheimer’s Disease?
In 2020, as many as 5.8 million Americans were living with Alzheimer’s disease.
Younger people may get Alzheimer’s disease, but it is less common.
The number of people living with the disease doubles every 5 years beyond age 65.
This number is projected to nearly triple to 14 million people by 2060.
Symptoms of the disease can first appear after age 60, and the risk increases with age.
What is known about Alzheimer’s Disease?
Scientists do not yet fully understand what causes Alzheimer’s disease. There likely is not a single cause but rather several factors that can affect each person differently.
Age is the best known risk factor for Alzheimer’s disease.
Family history—researchers believe that genetics may play a role in developing Alzheimer’s disease. However, genes do not equal destiny. A healthy lifestyle may help reduce your risk of developing Alzheimer’s disease. Two large, long term studies indicate that adequate physical activity, a nutritious diet, limited alcohol consumption, and not smoking may help people.
Changes in the brain can begin years before the first symptoms appear.
Researchers are studying whether education, diet, and environment play a role in developing Alzheimer’s disease.
There is growing scientific evidence that healthy behaviors, which have been shown to prevent cancer, diabetes, and heart disease, may also reduce risk for subjective cognitive decline.
What is the burden of Alzheimer’s disease in the United States?
Alzheimer’s disease is one of the top 10 leading causes of death in the United States.
The 6th leading cause of death among US adults.
The 5th leading cause of death among adults aged 65 years or older.
In 2020, an estimated 5.8 million Americans aged 65 years or older had Alzheimer’s disease. This number is projected to nearly triple to 14 million people by 2060.
In 2010, the costs of treating Alzheimer’s disease were projected to fall between $159 and $215 billion. By 2040, these costs are projected to jump to between $379 and more than $500 billion annually.
Death rates for Alzheimer’s disease are increasing, unlike heart disease and cancer death rates that are on the decline.
Dementia, including Alzheimer’s disease, has been shown to be under-reported in death certificates and therefore the proportion of older people who die from Alzheimer’s may be considerably higher.
For more science news stories check out our New Discoveries section at The Brighter Side of News.
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